降糖药的临床应用ppt课件.pptVIP

* 噻唑烷二酮类(TZD)与PPARr结合后,激活PPARr-RXR(视黄醇X受体)复合物，与DNA的的特定反应位点结合，启动与胰岛素敏感 相关的基因转录，既增加葡萄糖转运子4（GLUT4）、脂肪酸转运蛋白（FATP）、脂肪酸结合蛋白（aP2）脂蛋白脂酶（ENZ） 等物质的蛋白合成。从而增加葡萄糖和脂肪酸的摄取。 * 39 The traditional stepwise approach aims primarily to control acute symptoms. Dietary measures and exercise are not usually sufficient to control glycemia beyond the first year of therapy. If monotherapy with an OAD (oral anti-diabetic) proves inadequate, combination therapy is usually started. If this also proves unsuccessful, conversion to insulin is the next step, either alone or in combination with an oral agent. In the majority of cases, the stepwise approach does not lead to sustained control. Many physicians intensify treatment only when symptoms of poor glycemic control become apparent, rather than when glycemic targets are not reached. Campbell IW. Br J Cardiol 2000; 7:625–631. * 40 The early, aggressive approach to type 2 diabetes management avoids the risk of early treatment failure by adopting an intensive therapeutic strategy immediately upon diagnosis. Combinations of agents with complementary modes of action targeting the dual defects underlying type 2 diabetes (insulin resistance and ?-cell dysfunction) are most likely to support tight, long-term glycemic control. Furthermore, combination therapy with OADs (oral anti-diabetics), should be considered earlier in the regimen to provide additional glycemic control. Campbell IW. Br J Cardiol 2000; 7:625–631. * * 联合应用的剂量问题 * The Global Partnership for Effective Diabetes management 对于新诊断糖尿病患者早期联合治疗控制血糖达标提出如下建议： 诊断6个月内强化达标 HbA1c 6.5%*； 治疗3个月后, 如果患者没有达到目标 HbA1c 6.5%,* 考虑联合治疗； 诊断时 HbA1c ? 9% 的患者，起始即给予联合治疗； 作用机制互补的口服降糖药联合应用. *Or fasting/preprandial plasma glucose 110 mg/dL (6.0?mmol/L) where assessmentof HbA1c is not possible. 1Del Prato S, et al. Int J Clin Pract 2005; 59:1345–1355. * 正常人胰岛素分泌呈双相性： 第一时相：快速分泌相 ?细胞接受葡萄糖刺激,在0.5-1.0分钟的潜伏期后,出现快速分泌峰,呈尖锐高峰曲线，持续5-10分钟后减弱。快速分泌相反映?细胞储存颗粒中胰岛素的分泌 第二时相：延迟分泌相 葡萄糖进入细胞后，其代谢产物激活蛋白激酶，持续和增强胰岛素分泌，兴奋第二相胰岛素释放